Biomedical subjects

R G Tompkins

Publications and source records attributed to R G Tompkins.

189 records · Page 11Linked to original sources

PubMedDate not supplied

Energy and protein provisions for thermally injured children revisited: an outcome-based approach for determining requirements.

Energy and protein provisions for adequate wound healing and weight maintenance were examined among severely burned children. Actual intakes were documented for 27 patients admitted with a more than 40% total body surface area burn. Mean energy intake over the 4-week study period averaged 140% of the predicted basal metabolic rate (PBMR), and mean protein intake was 2.8 +/- 0.2 grams per kilogram daily. Wound healing progressed satisfactorily in all patients; at 4 weeks, the open wound area (% open) was 20% or less in 22 patients. Average weight at discharge was 88% +/- 2.6% of ideal body weight. Discharge weights were significantly higher (p < 0.05) among patients whose energy intake exceeded PBMR x 1.7 for at least 1 of the study weeks. We suggest that energy intakes approximating PBMR x 1.2 with a minimum of 3 grams of protein per kilogram will support adequate wound healing, whereas higher energy provisions (PBMR x 1.7) will enhance weight status.

Adolescent↗

PubMedDate not supplied

Cutaneous burn injury alters relative tricarboxylic acid cycle fluxes in rat liver.

Severe injury induces a hypermetabolic state in the liver; however, the pathways that are responsible for the increase in hepatic energy demand have not been identified. Relative fluxes in the tricarboxylic acid (TCA) cycle were determined in perfused livers from rats 4 days after administration of a cutaneous burn injury. The perfusate was supplemented with 5 mM uniformly labeled 13C-lactate to efficiently label intracellular metabolites. Flux ratios were calculated on the basis of (1) the 13C-labeling pattern of the glutamate and lactate isotopomers within the liver as determined by nuclear magnetic resonance spectroscopy and (2) an isotopomer mass balance model of the TCA cycle. Calculated flux ratios suggest that burn injury results in an increase in the contribution of pyruvate to the oxaloacetate pool at the expense of non-TCA cycle sources. Furthermore, a dramatic increase in 13C-labeling of glucose was observed in burned rat livers. These data taken together suggest that burn injury induces intrinsic changes in intrahepatic metabolism, including an alteration of the relative fluxes consistent with increased gluconeogenesis from lactate.

Animals↗

PubMedDate not supplied

Management of severe toxic epidermal necrolysis in children.

Toxic epidermal necrolysis (TEN) is a severe form of erythema multiforme that results in extensive epidermal sloughing; the condition is associated with a mortality of up to 70%. From 1991 to 1998, 10 children with severe toxic epidermal necrolysis were referred to a regional pediatric burn facility. Wounds were managed with strategy involving prevention of wound desiccation and superinfection, including the frequent use of biologic wound coverings. Children unable to guard their airway because of extensive oropharyngeal involvement were prophylactically intubated. Enteral nutrition was stressed. Steroids were not used and antibiotics were administered to managed specific foci of infection only. The 2 boys and 8 girls had an average age of 7.2+/-1.8 years (range 6 months to 15 years) and sloughed surface area of 76+/-6% of the body surface (range 50 to 95%). Antibiotics (3 children), anticonvulsants (3 children), nonsteroidals (2 children), and viral syndrome or unknown agents (2 children) were felt to have triggered the syndrome. Six children (60%) required intubation for an average of 9.7+/-1.8 days (range 2 to 14 days). Buccal mucosal involvement occurred in 9 (90%) and ocular involvement in 9 (90%). Although infectious complications were common (2 pneumonias, 2 urinary infections, 1 bacteremia, 2 central line infections, and 2 candidemias), all children survived after lengths of stay in the burn unit averaging 19+/-3 (range 6 to 40) days. The most common long-term morbidity was keratitis sicca (2 children, 20%), finger nail deformities (3 children, 30%), and variegated skin pigment changes (5 children, 50%). Although having both a cutaneous and visceral wound that predispose them to infectious complications, most children with TEN will survive if managed with a strategy emphasizing biologic wound closure, intensive nutritional support, and early detection and treatment of septic foci. Burn units have the resource set required to manage severe TEN and early referral of such children may have a favorable impact on survival.

Adolescent↗

PubMedDate not supplied

A 10-year experience with toxic epidermal necrolysis.

Toxic epidermal necrolysis is a devastating medication-induced desquamation disorder with a reported mortality rate of 30% to 60% in adults. Data from previously reported series suggest that age, delay in referral to a burn center, total body surface area (TBSA) involvement, and systemic steroid treatment are poor prognostic indicators. We reviewed the records of 39 patients treated in our burn center over the past 10 years and found that the mortality rate was significantly correlated with age, thrombocytopenia, and delay in presentation. Steroid treatment and TBSA involvement were not significantly related to the mortality rate. Thirty-nine adult patients with greater than 20% TBSA epithelial necrosis were cared for in our center from January 1987 to March 1998. Wounds were treated with topical antimicrobial medications and porcine xenografts in a bacteria-controlled nursing unit. We reviewed the records of these patients for 28 clinical characteristics and looked for clinical correlates of mortality by single analysis of variance. The mortality rate was 44% (17 of 39 patients); the cause of death was most commonly multiple-organ dysfunction syndrome, for which a microbial etiologic agent was not always identified. Autopsies were performed on 11 of the 17 patients who died; there was evidence of multiple-organ damage. The patients who survived and the patients who died did not differ significantly in TBSA epithelial necrosis (66%+/-6% vs 72%+/-5%, respectively), admission platelets, number of nosocomial infections, number of complications, preadmission exposure to steroids, or extent of mucosal involvement. When compared with the patients who died, the patients who survived were (1) 20 years younger (47.5+/-4.2 years vs 64.5+/-5.3 years), (2) admitted to the hospital sooner after the onset of their rash (3.5+/-0.4 days vs 5.9+/-1.0 days), (3) much less likely to experience early thrombocytopenia (platelet nadir, 154+/-24 vs 70+/-18), (4) more likely to be febrile on presentation, and (5) less likely to have been treated with antibiotics before referral to our unit. These differences were statistically significant. The most common etiologic agents were antibiotics, anticonvulsants, and nonsteroidal anti-inflammatory drugs. Our results for a group of older patients with toxic epidermal necrolysis with extensive skin involvement suggest that age, delay in hospitalization, thrombocytopenia, and early empiric antibiotic treatment are associated with a poor prognosis.

Adult↗

PubMedDate not supplied

Comparative evaluation of the quantitative utilization of parenterally and enterally administered leucine and L-[1-13C,15N]leucine within the whole body and the splanchnic region.

BACKGROUND: The purpose of this study was to quantify the kinetic aspects of leucine metabolism in the whole body and within the splanchnic region when an amino acid mixture is administered by the enteral route as compared with administration by the parenteral route. METHODS: Seven chronically catheterized dogs were studied during an intragastric infusion of L-[1-13C,15N]leucine with 0.24 g of complete amino acid mixture (kg-1.h-1) for 6 hours. The results are compared with those previously reported for nine dogs studied under essentially identical experimental conditions except that the tracer and amino acid mixtures were given by vein. RESULTS: At the whole body level, the various parameters of leucine metabolism (flux, oxidation, and disappearance into and release from proteins) were not significantly different among animals that were infused enterally and those that were infused parenterally. Leucine metabolism within the splanchnic region and gut was more extensive for enteral administration than for parenteral administration. For the splanchnic region, 31.4%, 27.9%, and 6.0% of enterally administered leucine was used for protein synthesis, deamination, and oxidization, respectively, compared with respective mean values of 19.5% (p < .001), 13.4% (p < .001), and 4.1% (p < .05) for parenterally administered leucine. For liver, 4.8% of enterally administered leucine was oxidized compared with 2.3% (p < .001) of parenterally administered leucine. These findings are qualitatively similar to those reported previously by us when comparing enteral and parenteral amino acid intakes but with an IV tracer infusion. CONCLUSION: Enteral administration seems to be more effective than an acute parenteral feeding regimen, at least in maintaining leucine (protein) balance in gut tissues.

Amino Acids↗

PubMedDate not supplied

Maximal parenteral glucose oxidation in hypermetabolic young children: a stable isotope study.

BACKGROUND: During periods in which nutrition support of critically ill young children must be parenteral, glucose infusions are administered at up to 10 or more mg.kg-1.min-1 to meet predicted energy needs. However, data in adults suggest that such high glucose loads exceed the ability to oxidize glucose in the hormonal milieu that characterizes critical illness. The purpose of this study was to determine if these high glucose loads are oxidized by critically ill young children. METHODS: Ten young children with serious burns were enrolled in a stable isotope study of glucose metabolism. These five boys and five girls were an average age of 5.2 years (range, 1 to 11 years), weight of 18.4 kg (range, 10 to 31 kg) and burn size of 51.6% of the body surface (range, 35% to 86%). During clinically required episodes of parenteral nutrition support, we used the [13C6]glucose tracer to assess the efficacy of glucose oxidation at both 5 and 8 mg.kg-1.min-1. Serum glucose was recorded and indirect calorimetry was performed. RESULTS: The fraction of exogenous glucose oxidation fell from 59% +/- 5% to 47% +/- 5% (p < .05). Although there was a significantly increased level of total glucose oxidation (3.2 to 3.8 mg.kg-1.min-1), this increment (29% +/- 9%) was accompanied by a significant decrease in the efficiency of energy production, because the bulk of the additional glucose above 5 mg.kg-1.min-1 was not being oxidized. Plasma glucose concentration did not change (145 +/- 4 vs 137 +/- 4 mg/dL, p < .01) and whole-body expired gas respiratory quotients remained consistent with a mixed fuel oxidation, implying that there exists an increased rate of exogenous glucose uptake by tissues in nonoxidative pathways. CONCLUSIONS: Maximum glucose oxidation in severely burned children occurs at intakes approximating 5 mg.kg-1.min-1. Exogenous glucose in excess of this amount enters nonoxidative pathways and is unlikely to improve energy balance. Clinical markers such as serum glucose levels or expired respiratory quotient may not detect inefficient glucose utilization.

Acute Disease↗

PubMedDate not supplied

The metabolic basis of the increase of the increase in energy expenditure in severely burned patients.

BACKGROUND: Severe burn trauma is characterized by an elevated rate of whole-body energy expenditure. APPROACH: In this short review, we have attempted to assess the metabolic characteristics of and basis for the persistent increase in energy expenditure during the flow phase of the injury. We consider some aspects of normal energy metabolism, including the contribution of the major adenosine triphosphate (ATP)-consuming reactions to the standard or basal metabolic rate. Rate estimates are compiled from the literature for a number of these reactions in healthy adults and burned patients, and the values are related to the increased rates of whole-body energy expenditure with burn injury. RESULTS: Whole-body protein synthesis, gluconeogenesis, urea production, and substrate cycles (total fatty acid and glycolytic-gluconeogenic) account for approximately 22%, 11%, 3%, 17%, and 4%, respectively, of the burn-induced increase in total energy expenditure. CONCLUSIONS: These ATP-consuming reactions, therefore, seem to explain approximately 57% of the increase in energy expenditure. The remainder of the increase may be due, in large part, to altered Na(+)-K(+)-ATPase activity and increased proton leakage across the mitochondrial membrane.

Adenosine Triphosphate↗

PubMedDate not supplied

A device to measure the oxygen uptake rate of attached cells: importance in bioartificial organ design.

Quantification of the dependence of cellular oxygen uptake rate (OUR) on oxygen partial pressure is useful for the design and testing of bioartificial devices which utilize cells. Thus far, this information has only been obtained from suspended cells and from cells attached to microcarriers. In this work, a device was developed to obtain the dependence of OUR on oxygen partial pressure for anchorage-dependent cells cultured in standard culture dishes. The device is placed and sealed on the top of the culture dish, and holds a Clark polarographic mini-electrode flush with the bottom surface of the device. It also houses a motor to spin a magnetic stir bar within the cell chamber to insure that the medium is well-mixed. Several characteristics of the device--such as oxygen leakage into the device chamber, electrode-lag time, and linearity of the electrode at low oxygen partial pressures--were quantified and their potential effect on the values of Vm (maximal OUR) and K0.5 (oxygen partial pressure at which OUR is half-maximal) were evaluated. Comparison of Vm and K0.5 values obtained with this device with previously published values for suspended rat hepatocytes, Bacillus cereus, and E. coli indicated that the technique provides values accurate within 30% as long as the cell under study has a K0.5 greater than approximately 1.0 mmHg. For hepatocytes cultured on 0.05 mm thickness collagen gel for 1 day (n = 4) and 3 days (n = 6), Vm was found to be 0.38 +/- 0.12 and 0.25 +/- 0.09 nmol O2/S/10(6) cells, respectively, and K0.5 was found to be 5.6 +/- 0.5 and 3.3 +/- 0.6 mmHg, respectively. This technique should aid in predicting bioreactor conditions such as flow rate, cell density, distance of cell from flow, and gas phase oxygen partial pressure which can lead to oxygen limitations. In addition, further studies of the effect of factors such as extracellular matrix composition, metabolic substrate, and drugs on the dependence of OUR on oxygen partial pressure for many anchorage-dependent cell types can be pursued with this technique.

Animals↗

PubMedDate not supplied

Ice formation in isolated human hepatocytes and human liver tissue.

Cryopreservation of isolated cells and tissue slices of human liver is required to furnish extracorporeal bioartificial liver devices with a ready supply of hepatocytes, and to create in vitro drug metabolism and toxicity models. Although both the bioartificial liver and many current biotoxicity models are based on reconstructing organ functions from single isolated hepatocytes, tissue slices offer an in vitro system that may more closely resemble the in vivo situation of the cells because of cell-cell and cell-extracellular matrix interactions. However, successful cryopreservation of both cellular and tissue level systems requires an increased understanding of the fundamental mechanisms involved in the response of the liver and its cells to freezing stress. This study investigates the biophysical mechanisms of water transport and intracellular ice formation during freezing in both isolated human hepatocytes and whole liver tissue. The effects of cooling rate on individual cells were measured using a cryomicroscope. Biophysical parameters governing water transport (Lpg = 2.8 microns/min-atm and ELp = 79 kcal/mole) and intracellular heterogeneous ice nucleation (omega het = 1.08 x 10(9) m-2s-1 and kappa het = 1.04 x 10(9) K5) were determined. These parameters were then incorporated into a theoretical Krogh cylinder model developed to simulate water transport and ice formation in intact liver tissue. Model simulations indicated that the cellular compartment of the Krogh model maintained more water than isolated cells under the same freezing conditions. As a result, intracellular ice nucleation occurred at lower cooling rates in the Krogh model than in isolated cells. Furthermore, very rapid cooling rates (1000 degrees C/min) showed a depression of heterogeneous nucleation and a shift toward homogeneous nucleation. The results of this study are in qualitative agreement with the findings of a previous experimental study of the response to freezing of intact human liver.

Cell Communication↗